📊 Definition & Approach
• Precocious puberty: onset of secondary sexual characteristics before age 9 years in boys
• Isosexual vs heterosexual (feminization)
• Central (gonadotropin-dependent): premature activation of hypothalamic-pituitary-gonadal axis → pubertal FSH/LH levels
• Peripheral (gonadotropin-independent): low FSH/LH, sex steroids from testes or adrenals
🧠 Central Precocious Puberty (CPP)
• Idiopathic (most common, especially boys). MRI brain indicated (rule out hypothalamic hamartoma, tumor)
• Hypothalamic hamartoma: most common CNS lesion causing CPP, often with gelastic seizures
• Other: optic glioma (NF-1), post-inflammatory, post-irradiation, hydrocephalus
🩸 Peripheral Precocious Puberty (Gonadotropin-Independent)
• Testotoxicosis (familial male-limited): activating mutation of LH receptor, testosterone elevated, FSH/LH prepubertal, presents age 2-3
• Congenital adrenal hyperplasia (CAH): 21-hydroxylase deficiency → elevated 17-OHP, DHEAS, testosterone, ± salt wasting
• hCG-secreting tumor: hepatoblastoma, germinoma, teratoma, choriocarcinoma → stimulates testosterone production, small testes
• Leydig cell adenoma: unilateral testicular mass, elevated testosterone, prepubertal FSH/LH
📋 Other Causes
• McCune-Albright syndrome: cafe-au-lait spots (coast of Maine), polyostotic fibrous dysplasia, peripheral precocious puberty (more common in girls)
• Hypothyroidism (Van Wyk-Grumbach): rare; delayed bone age (not advanced), elevated TSH cross-reacts with FSH receptor → testicular enlargement without testosterone elevation, treated with levothyroxine
• Exogenous androgens: creams, gels, supplements
📌 Decision strategy: GnRH agonist stimulation test distinguishes central (pubertal LH response) from peripheral (prepubertal LH response). Advanced bone age is hallmark of precocious puberty; but hypothyroidism causes precocious puberty with delayed bone age.